Anakinra Therapy for Non-cancer Inflammatory Diseases.
Anakinra Therapy for Non-cancer Inflammatory Diseases.
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DOI：
10.3389/fphar.2018.01157
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发表时间：
2018
影响因子：
5.6
通讯作者：
Dinarello CA
中科院分区：
文献类型：
--
作者：
Cavalli G;Dinarello CA
白细胞介素-1 (IL-1) 是典型的炎症细胞因子：两种不同的配体（IL-1α 和 IL-1β）结合 IL-1 1 型受体 (IL-1R1) 并诱导大量次级炎症介质，包括前列腺素、细胞因子和趋化因子。 IL-1α 在内皮细胞和上皮细胞中组成型存在，而 IL-1β 在骨髓细胞中可诱导，并在 caspase-1 裂解后释放。在过去的 30 年里，IL-1 介导的炎症已在多种疾病中得到证实，从罕见的自身炎症性疾病到痛风和类风湿性关节炎 (RA)、2 型糖尿病、动脉粥样硬化和急性心肌梗死等常见疾病。阻断 IL-1 的阿那白滞素进入临床舞台，阿那白滞素是天然存在的 IL-1 受体拮抗剂 (IL-1Ra) 的重组形式； IL-1Ra 阻止 IL-1α 以及 IL-1β 与 IL-1R1 的结合。抑制 IL-1 介导的炎症可以防止组织损伤和器官功能障碍的有害后果。尽管阿那白滞素目前被批准用于治疗 RA 和冷热蛋白相关周期性综合征，但阿那白滞素的超说明书使用远远超出了其批准的适应症。皮下注射 100 毫克阿那白滞素可在几天内提供临床上明显的益处，对于某些疾病，阿那白滞素每天使用已超过 12 年。与其他生物制剂相比，阿那白滞素具有无与伦比的安全性：即使在有潜伏感染重新激活风险的人群中，机会性感染，特别是结核分枝杆菌感染也很少见。由于其优异的安全性和相对较短的作用持续时间，阿那白滞素还可用作 IL-1 介导的未明确疾病的诊断工具。尽管阿那白滞素目前正处于治疗癌症的临床试验中，但本次综述的重点是阿那白滞素治疗急性和慢性炎症性疾病。
Interleukin-1 (IL-1) is the prototypical inflammatory cytokine: two distinct ligands (IL-1α and IL-1β) bind the IL-1 type 1 receptor (IL-1R1) and induce a myriad of secondary inflammatory mediators, including prostaglandins, cytokines, and chemokines. IL-1α is constitutively present in endothelial and epithelial cells, whereas IL-1β is inducible in myeloid cells and released following cleavage by caspase-1. Over the past 30 years, IL-1-mediated inflammation has been established in a broad spectrum of diseases, ranging from rare autoinflammatory diseases to common conditions such as gout and rheumatoid arthritis (RA), type 2 diabetes, atherosclerosis, and acute myocardial infarction. Blocking IL-1 entered the clinical arena with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist (IL-1Ra); IL-1Ra prevents the binding of IL-1α as well as IL-1β to IL-1R1. Quenching IL-1-mediated inflammation prevents the detrimental consequences of tissue damage and organ dysfunction. Although anakinra is presently approved for the treatment of RA and cryopyrin-associated periodic syndromes, off-label use of anakinra far exceeds its approved indications. Dosing of 100 mg of anakinra subcutaneously provides clinically evident benefits within days and for some diseases, anakinra has been used daily for over 12 years. Compared to other biologics, anakinra has an unparalleled record of safety: opportunistic infections, particularly Mycobacterium tuberculosis, are rare even in populations at risk for reactivation of latent infections. Because of this excellent safety profile and relative short duration of action, anakinra can also be used as a diagnostic tool for undefined diseases mediated by IL-1. Although anakinra is presently in clinical trials to treat cancer, this review focuses on anakinra treatment of acute as well as chronic inflammatory diseases.
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影响因子：
10.9
作者：
Belani, Hrishikesh;Gensler, Lianne;Leslie, Kieron S.
通讯作者：
Leslie, Kieron S.
影响因子：
3.4
作者：
Ahmadi, Neda;Brewer, Carmen C.;Kim, H. Jeffrey
通讯作者：
Kim, H. Jeffrey
影响因子：
27.4
作者：
Bodar, E. J.;Kuijk, L. M.;Frenkel, J.
通讯作者：
Frenkel, J.
影响因子：
1.4
作者：
Berenise Gamez-Gonzalez, Luisa;Moribe-Quintero, Isabel;Yamazaki-Nakashimada, Marco
通讯作者：
Yamazaki-Nakashimada, Marco
DOI：
10.1056/nejmoa0807865
发表时间：
2009-06-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Aksentijevich I;Masters SL;Ferguson PJ;Dancey P;Frenkel J;van Royen-Kerkhoff A;Laxer R;Tedgård U;Cowen EW;Pham TH;Booty M;Estes JD;Sandler NG;Plass N;Stone DL;Turner ML;Hill S;Butman JA;Schneider R;Babyn P;El-Shanti HI;Pope E;Barron K;Bing X;Laurence A;Lee CC;Chapelle D;Clarke GI;Ohson K;Nicholson M;Gadina M;Yang B;Korman BD;Gregersen PK;van Hagen PM;Hak AE;Huizing M;Rahman P;Douek DC;Remmers EF;Kastner DL;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R